Methylene-disalicylic acid derivative



Patented Jan. 14, 1930 PATENT OFFICE SAMUEL LEWIS SUMMERS, F FORT WASHINGTON, PENNSYLVANIA mnrmmtn-nisamovnrc non) DERIVATIVE Ho Drawing.

My invention relates to or anic compounds and their manufacture and 1s especially concerned with novel condensation products of pyruvic acid with the di (aminobenzyl) ethers of methylene-disalicylic amide, useful for pharmaceutical purposes, as hereinafter described.

My products may be prepared as follows:

Starting with methylene-disalicylic acid, the first step is esterification, preferably by ethyl alcohol, though other alcohols may be used. As the alcohol is replaced in the next step, the particiilar alcohol employed is of no influence on the final product. The esterification may be accomplished as follows, though I do not limit myself to this particular method:

Dissolve 288' pounds of methylene-disalicylic acid in 150 pounds of ethyl alcohol 0 and slowly add to this solution, keepin the temperature below 75. C., 100 pounds 0 concentrated sulphuricacid. When all of this has been added, heat to 150 C. under a reflux condenser for two hours. The essential product is the diethyl ester of methylene-disalicylic acid:

CH (0 H, (OH) CONH-z') 2,

as the essential product. It is immaterial whether this amide is obtained through the ester as described or from methylene-disalicylic acid by some other method.

The third main step is to substitute nitro- 50 benzyl groups in the two hydroxyl groups of Application filed October 12, 1928. Serial No. 312,200.

the above described amide. One practicable way of accomplishing this, to which I do not limit myself, is as follows: 286 pounds of methylene-disalicyl-amide is mtimately mixed with 345 pounds of p-nitrobenzyl chloride and 250 pounds of sodium carbonate and heated for twenty-four hours to 130 C. The essential product is a di(nitrobenzyl) ether of methylene-disalicyl amide:

CsHa(OOHaOoH4N0g)CONH| 016 omuoomoamnoaconm di (nitrobenzyl) substitution product with 400 ounds of free metallic zinc preferably in the orm of dust, and 1800 pounds of hydrochloric 0 acid. After the heat of the spontaneous chemical reaction has subsided the mass is heated to 0. and maintained at that temperature for eight hours. The mixture is made slightly alkaline by the addition of ammonia water, which causes the separation of the desired diamino derivative, which is filtered off and washed with water to free it from the zinc chloride producedin the reaction. The product is dissolved in alcohol and freed from an zinc salts that may remain b saturating t is solution with hydrogen su phide. The alcohol is eliminated b eva oration, which leaves the essential pro not w ich is a di(aminobenzy1) ether of methylene-disalicyl w amide:

lmwommmNHnoo n. as"

The fifth main step is to introduce pyruvyl loo groups into the four -NI-I groups of the above described compound. One wa of accomplishing this, to which I do not limit myself, is as fo lows Heat 496 ounds of the di(aminobenzyl) ether of met ylene-disalicyl amide with 350 pounds of pyruvic acid, previously dissolved in alcohol, to for eight hours. The essential product is a condensation product having the structural formula:

H CoHKOCHNaHNHOOCOOHQOONHCOOOCH G This is a crystalline solid, insoluble in.

water but soluble in alcohol. In case the reaction is not pushed to completion, less than four molecules of pyruvic acid may react,

giving products containing two or three.

pyruvyl groups instead of four. The% prodnets are similar in properties and may be used for the same pharmaceutical purposes.

Having thus described my invention, I claim:

The hereindescribed condensation product of a di(aminobenzyl) ether of meth lenedisalicyl amide with pyruvic: acid, typi ed by the formula CuHa(OCH2OaH4NER)CONHR CH1 wherein It may represent the pyruvyl group or hydrogen, but having at least two Rs as pyruvyl groups, and insoluble in water but soluble in alcohol.

In testimony whereof, I have hereunto signed my name at Ambler, Pennsylvania, this 9th day of October, 1928,

SAMUEL LEWIS SUMMERS.

rmaeez 

